The field of the invention is the treatment of neuropathy. More specifically, the invention relates to the use of photo-energy treatment of neuropathy such as peripheral neuropathy, diabetic neuropathy, post-polio syndrome, small fiber neuropathy, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), wherein the neuropathy is treated and the sensory impairment of the patient is reduced.
Neuropathy is a general term denoting functional disturbances and/or pathological changes in the peripheral nervous system. If the involvement is in one nerve it is called mononeuropathy, in several nerves, mononeuropathy multiplex, and if diffuse and bilateral, polyneuropathy. The etiology may be known, for example, arsenical neuropathy, diabetic neuropathy, ischaemic neuropathy or traumatic neuropathy, or it may be unknown.
Diabetic peripheral neuropathy is a consequence, in part, of diabetes mediated impairment blood flow to, and resultant hypoxia of nerves. The condition results in sensory impairment. Prior to the present invention, there was no known treatment for reversing the sensory impairment of this disease manifestation, although some treatments, such as capsiacin cream, tricyclic antidepressants, and valproic acid are efficacious in diminishing pain. Other studies have demonstrated some increase in conduction velocity with use of aldose reductase inhibitors. Insulin pumps or pancreas transplantation which reduce the hyperglycemia of diabetes are sometimes effective in slowing the progress of diabetic neuropathy. With each of these approaches there have been notable problems in feasibility, logistics, and efficacy, so that additional research into preventing/treating diabetic neuropathy has become a major research focus of the Juvenile Diabetes Foundation, the American Diabetes Association, and the National Institutes of Health.
Impaired sensation in the feet becomes evident to the patient and clinician several years after the onset of diabetes and, importantly, does not spontaneously regress. In other words, diabetic peripheral neuropathy is considered to be a progressive disease. Ultimately the loss of feeling can result in one or more ulcerations of the foot or feet. If the degree of sensory impairment reaches a level of 5.07 or higher, using the Semmes Weinstein monofilament test, there is a very high likelihood of ulceration, followed by amputation. Treatments that reduce sensory impairment may minimize the risk of the onset of ulcerations that often lead to amputations. Additionally, reduced sensory impairment may improve proprioception and balance, thereby reducing the likelihood of injurious falls.
Several products expected to reduce sensory impairment due to diabetic neuropathy, including nerve growth factor and aldose reductase inhibitors, in large clinical trials, have failed to meet full expectations of clinicians or patients. Prior to the present invention, there was no effective therapy available for reducing sensory impairment associated with diabetic neuropathy.
A number of pharmaceutical approaches have been taken to treat neuropathy, using medicaments to alleviate the symptoms. U.S. Pat. No. H1,899 to, Bhat, et al. discloses a method for determining a concentration of insulin-like growth factor-I (IGF-I) that defines a therapeutically effective dose of IGF-I. The patent discloses a dose that provides a therapeutic response in the treatment of neurological disorders for which IGF-I is utilized (including peripheral neuropathy, diabetic neuropathy, post-polio syndrome, small fiber neuropathy, arterial lateral sclerosis, and multiple sclerosis). The method comprises determining whether a particular dose of IGF-I causes a 1.5 fold or greater increase in the homeostatic concentration of plasma insulin-like growth factor binding proteins-2 (IGFBP-2) in a mammal that has previously received a defined dose of IGF-I. The method of the invention can also be used to determine whether or not biological tolerance has developed to a particular dose of IGF-I.
U.S. Pat. No. 6,087,392 to Reiter discloses a compound of (4-arylsulfonylamino)-tetrahydropyran-4-carboxylic acid hydroxamides which is useful in the treatment of a condition selected from the group of diseases including peripheral neuropathy. U.S. Pat. No. 6,075,053 to Hausheer discloses a method of treating patients afflicted with peripheral neuropathy by administering to a patient an effective amount of a thiol or reducible disulfide compound according to the formula set forth in the specification. U.S. Pat. No. 5,567,724 to Kelleher, et al. discloses a method of treating peripheral neuropathy using acid or alkaline phosphatase inhibitors.
U.S. Pat. Nos. 4,927,849 and 5,066,676 respectively to Caccia, et al. discloses sulfonamido derivatives having the property of inhibiting the aldose reductase enzyme system. Specific derivatives include xanthosulfonamido and benzensulfonamido derivatives, which are useful in the treatment of the complications induced by diabetes, such as those involving the eyes. The derivatives are also useful in the treatment of peripheral neuropathy.
All of the above patents require the patient to take pharmaceuticals or drugs, which involves ongoing treatments and possible side-effects. None of the above references teach or suggest the treatment of a patient having neuropathy that does not involve the use of pharmaceuticals or drugs, as does the present invention.
U.S. Pat. No. 4,930,504 discloses an array of a substantially monochromatic radiation source such as light-emitting diodes of a plurality of wavelengths, preferably three wavelengths, to treat inflammations, wounds, burns, chronic ulcerations including diabetic ulcers, deficient circulation, pain, nerve degeneration, eczema, shingles, infection, scars, acne bone fractures, muscle and ligament injuries, arthritis, osteo-arthritis, rheumatoidal arthritis, skin grafts, gingival irritation, oral ulcers, dental pain and swelling, cellulitis, stretch marks, skin tone, alopecia areata, trigeminal neuralgia, herpes, zosten, sciatica, cervical erosions and other conditions. However, this patent does not disclose that a photo-energy source may be capable of reducing sensory impairment associated with neuropathy.
The use of monochromatic infrared energy has been successfully used to treat recalcitrant dermal lesions, including venous ulcer, diabetic ulcers, and a wound related to scleroderma. (Horwitz, L. R., Advances in Wound Care, January/February, 1999). U.S. Pat. No. 5,358,503 discloses a device for the treatment of skin and subcutaneous structures with photo-energy and * therapeutic heat. The device includes a flexible pad which holds diodes in juxtaposed position with each other. Neither the Horwitz article nor U.S. Pat. No. 5,358,503, disclose the use of an apparatus for the reduction of sensory impairment associated with neuropathy.
None of the above references disclose the present invention involving the use of an apparatus for photo-energy treatment for reducing sensory impairment due to neuropathy.
The present invention is a method for the reduction of sensory impairment due to peripheral neuropathy comprising placing an apparatus which provides photo-energy in proximity to the skin and/or subcutaneous structures suffering from sensory impairment, arid irradiating the skin and/or subcutaneous structures with the apparatus with sufficient duration. (total weeks of treatments), intensity (energy in Joules per treatment) and frequency (treatments per week) to reduce sensory impairment. The reduction in sensory impairment can be measured by the Semmes Weinstein test and/or other diagnostic-type test of sensory impairment. Optionally, the apparatus may also deliver therapeutic heat so that the treatment area of the skin and the adjacent subcutaneous structure of the patient receive photo energy treatment and thermal treatment simultaneously or selectively.
A variety of apparatuses can be used to generate the photo-energy needed for treatments that reduce sensory impairment. The preferred apparatus for photo-energy treatment is a plurality of diodes, defining a treatment area, each diode having a longitudinal axis and being capable of projecting a non-coherent cone of photo-energy when energized. The cone of photo-energy from each diode overlaps the cone of photo-energy from each other diode, so that the photo-energy completely covers the treatment area. The apparatus has a means for holding each of said diodes in position with each other and in proximity of the skin in substantially perpendicular relationship to said longitudinal axis.
Such means include a flexible resin-based pad, such as a polyacrylate pad, an interconnecting flexible mesh pad, a woven cloth-like material pad, a deformable matrix, such as modeling clay which can conform to an extremity, a castable material which hardens to a desired shape, or a flexible elongated strip of cloth or resin-based material that can be wrapped around a digit or directed to a small, narrow area.
The apparatus has means connected to the diodes for activating them. Such means includes switches, such as manually activated switches, and electronic switches, such as solenoids, which can be activated manually, or electronically, such as by a microprocessor. The present invention includes using an apparatus, wherein the apparatus is attached to a microprocessor which is programmed to activate and deactivate the apparatus.
Optionally, the apparatus may also deliver therapeutic heat so that the treatment area of the skin and the adjacent subcutaneous structure of the patient receive photo-energy treatment and thermal treatment simultaneously or selectively. The means for heating includes the diodes themselves, wherein the heating provided is increased with the current provided. Further heating can be provided by resistance heating, such as by resistors or heating elements. The preferred apparatus for photo-thermal treatment is described in detail in U.S. Pat. No. 5,358,503, which is hereby incorporated by reference.
Sensory impairment can be measured by a variety clinical diagnostic of tests. The most common test is the Semmes Weinstein test, where pressure is applied against the skin of affected areas using monofilaments of varying thicknesses to determine the level of sensory impairment. Other methods of determining sensory impairment include the hot-versus-cold test which is used to test sensory impairment to temperature change. The vibratory test is used to test sensory impairment to a vibrating tuning fork. The nerve conduction velocity test (NCV) measures sensory impairment by evaluating the conductivity of nerves, as does the needle electromylagram test (EMG). The quantitative sensory test gives a two point discrimination test of sensory impairment. The Romberg test is used to determine gross sensory impairment of the lower extremities as it affects balance, and the Balance Master is a device that measures gross sensory impairment of the lower extremities affecting balance in more objective terms. Other quantitative tests of sensory impairment due to neuropathy may be employed or developed in the future. Any one of these tests, alone or in combination could indicate sensory impairment resulting from neuropathy. A preferred diagnostic test is the Semmes Weinstein monofilament test.
The present method involves a sequential treatment, wherein a patient is treated at a frequency of from about one to fourteen times each week for a period of about from about five to sixty minutes a treatment. Transitory response may be observed after one treatment and longer lasting response may require additional treatments, which, in neuropathy due to a chronic condition, may be required for a period coextensive with the remainder of the patient""s life. A preferred frequency is from about one to fourteen treatments weekly with a duration of from ten to fifty minutes. The total number of treatments can range from about one to 150. The patient is treated for a duration of from about one to twelve weeks. A preferred range of duration is from about two to ten weeks. The frequency and duration of treatment, as well as the total number of treatments, depends, in part, on the severity and duration of the neurological impairment as Well as the chronicity of the underlying causation of neuropathy.
The intensity of the treatment can be changed by varying the Joules of photo-energy delivered to the treatment site. Typically, from about 1450 to about 6500 Joules are delivered per affected extremity per treatment, however, fewer Joules per treatment delivered more frequently, i.e., a lower intensity with a higher frequency, may be equally effective.
The intensity of the photo-energy delivered in a treatment is calculated as the Joules per treatment. It is calculated as the product of the energy (Joules) per area (cm2) per minute emitted by the photo-energy device, the treatment area (cm2), and the length (minutes) of treatment. Variance in the energy emitted by the photo-energy device, the treatment area (cm2), and the length of treatment (minutes) will accordingly change the intensity of the photo-energy delivered as measured in Joules per treatment. The preferred photo-energy device delivers about 1.15 Joules per cm2 per minute (J/cm2/min) over the defined treatment area of about 22.5 cm2. As many as eight photo-energy devices may be used simultaneously to provide a treatment area of up to 180 cm2. Thus, a treatment using from one to eight photo-energy devices will yield a range of from about 26 to about 207 Joules per minute of treatment. Using a treatment time of about 30 minutes, the intensity of treatment would be from about 780 to about 6240 J/treatment. The intensity of the treatment of the present invention is in the range of from about 500 to about 7000 J/treatment. A preferred range is from about 500 to about 5000 J/treatment. A most preferred range is from about 1500 to about 5000 J/treatment.
The present invention further embodies the use of the above method in a prophylactic manner, so as to prevent a neurological deficit in patients afflicted with progressive chronic conditions, such as diabetes, from which neuropathy is known to eventually occur. In such circumstances, the treatment of chronic conditions will have a duration that spans the life of the patient. Alternatively, the treatment maybe subsequent to an initial series of treatments, and long-term to prevent the re-occurrence of sensory impairment, with the duration ranging up to the life-span of the patient.